ES2519540T3 - Compressed pharmaceutical compositions comprising PEG and electrolytes - Google Patents

Abstract

The invention provides a compressed pharmaceutical composition comprising - polyethylene glycol of molecular weight from 2000 to 4500, wherein the polyethylene glycol makes up from 80 to 99.5% by weight of the composition, and - one or more electrolytes. The compressed pharmaceutical composition of the invention comprising polyethylene glycol has been found to have a more agreeable taste and a more agreeable mouthfeel than previously proposed liquid or dry powder or granular compositions.

Description

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DESCRIPTION

Compressed pharmaceutical compositions comprising PEG and electrolytes

The present invention relates to compositions for the treatment of constipation, fecaloma, fecal retention, gas and intestinal cramps, flatulence, and also to compositions for orthostatic washing, colon evacuation or colon cleansing. The invention relates in particular to compositions for the treatment of constipation. The invention further relates to methods of using such compositions.

General Background

Constipation is a generalized condition that usually results in discomfort. The physical presence of retained feces in the colon and / or rectum leads to a feeling of general malaise and headaches. In extreme cases of prolonged constipation may result in dyskecia of the presence of scallops or fecalites in the rectum.

Numerous constipation treatments have been developed, including dietary manipulation (for example, increasing the fiber content of the diet and removing foods that are considered to be the cause of constipation), laxatives and enemas. Laxatives are agents that promote and help with defecation. Osmotic laxatives act by retaining water in the colonic light, thus counteracting the normal dehydrating action of the colon. By suppressing the dehydration action of the colon, the osmotic laxative produces a fecal current that is softer, more bulky and easier to expel.

Several treatments of osmotic laxatives currently in use include polyethylene glycol (PEG). Such compositions may also include electrolytes. A laxative comprising PEG and electrolytes that is currently on the market is Movicol®. Movicol is available in the UK and other Norgine Limited countries (Chaplin House, Widewater Place, Moorhall Road, Harefield, Middlesex UB9 6NS, RU). It is supplied in sachets, each containing 13.8 g of powder. Each envelope contains the following components: Macrogol (polyethylene glycol) 3350: 13,125 g, sodium chloride: 350.7 mg; sodium bicarbonate: 178.5 mg; potassium chloride: 46.6 mg; and flavoring and sweetener (trace amounts). The envelopes include instructions for constituting the powder in 125 ml of water.

Many patients taking Movicol or other PEG-based laxatives in powder, granular, solution or suspension form find the taste unpleasant and salty. Those negative feelings lead to patient compliance being adversely affected.

Colon cleansing is important before numerous diagnostic and surgical procedures, for example, before colonoscopy, barium enema examination or colon surgery. It is also useful to prevent infection after surgery in the large intestine. Colon cleansing is also known as colon unclogging.

A colon cleansing procedure is orthostatic bowel lavage, in which a large volume of an electrolyte solution is ingested, both by drinking it and by infusion using a nasogastric tube. Such washing solutions are also known as bowel solutions. The consumption of the solution produces volume-induced diarrhea and thus cleansing the colon. The most commonly used wash solutions include PEG. In 1980, Davis and colleagues reported the development of a wash solution, which they described as being associated with absorption

or minimal secretion of water and electrolyte (Davis G.R. et al., Gastroenterology, 1980, 78, 991-995). The solution included sodium sulfate and polyethylene glycol. In addition to sodium sulfate (40.0 mM, 5.68 g / l) and polyethylene glycol (PEG 4000 "carbowax", 64 g / l), the solution described by Davis et al. it comprises sodium chloride (25 mM, 1,463 g / l), potassium chloride (10 mM, 0.745 g / l), sodium bicarbonate (20 mM, 1,680 g / l) and water. The solution was administered in an amount of 4 liters and was shown to be effective in cleaning the gastrointestinal tract. A related solution has been marketed under the trade name GoLYTELY® (Braintree Laboratories Inc, Braintree, Massachusetts, USA).

The commercially available GoLYTELY® composition, as available after August 1996 and at the time of presentation, is supplied as a dry powder comprising sodium sulfate (40.0 mM, 5.685 g / l), sodium chloride ( 25 mM, 1,464 g / l), potassium chloride (10 mM, 0,743 g / l), sodium bicarbonate (20 mM, 1,685 g / l) and PEG 3350 polyethylene glycol (59 g / l) to prepare up to 4 liters. GoLYTELY® is also supplied in aqueous solution.

As with laxative compositions, many patients taking GoLYTELY® or other cleaning solutions based on PEG find the taste of the solutions unpleasant. Those negative feelings lead to patient compliance being adversely affected.

The fecaloma, also known as fecal retention, is the formation of a firm intransitable mass of feces in the rectum

or distal colon. The fecaloma is frequently treated using procedures similar to those described above for constipation and colon cleansing. A larger dose is usually needed than in the case of constipation treatment. Therefore, the recommended treatment using Movicol comprises taking 8 sachets of Movicol (each containing the amounts of components mentioned above) per day dissolved in 1 liter of water and

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Drink it within 6 hours, usually for up to 3 days.

As with laxative and cleaning compositions, many patients taking Movicol® or other PEG-based compositions for fecaloma find the taste of the solutions unpleasant. Those negative feelings lead to the compliance of a patient being adversely affected.

Therefore, there is still a requirement for laxatives, fecaloma treatments and washing preparations with a more pleasant (less salty) taste and a more pleasant mouthfeel.

Description of the invention

The invention provides a compressed pharmaceutical composition comprising

-

polyethylene glycol of molecular weight from 2000 to 4500, in which the polyethylene glycol constitutes from 80 to 99.5% by weight

of the composition,

-

one or more electrolytes

for the treatment of constipation, fecaloma, fecal retention, gas and intestinal cramps, or flatulence; or for orthostatic lavage, bowel movement or colon cleansing. In particular, such a composition is provided for use in the treatment of constipation, fecaloma, fecal retention, gas and intestinal cramps, flatulence. A composition of the invention is also provided for orthostatic washing, colon evacuation or colon cleansing.

It has surprisingly been found that a compressed pharmaceutical composition comprising PEG, for example, a solid tablet, is significantly tastier than the previously proposed compositions and is effective when administered. It has been found that the compressed pharmaceutical composition of the invention comprising polyethylene glycol has a more pleasant taste and a more pleasant mouthfeel than the previously proposed dry or granular liquid or powder compositions.

In the compressed pharmaceutical compositions of the invention, polyethylene glycol constitutes 80 to 99.5% by weight of the composition. The rest of the composition consists of electrolytes and optionally one or more components selected from excipients, sweeteners and flavorings.

The polyethylene glycol (PEG) used in a composition of the present invention preferably has an average molecular weight of 2000 or greater. Preferably, the PEG has an average molecular weight of 2500 or greater. Preferably, the PEG has an average molecular weight of 4500 or less. For example, the PEG can be PEG 3350

or PEG 4000. PEG 3350 is the most preferred. This product is commercially available, for example, from Dow Chemical Co., Clariant GmbH or BASF under the trade name Macrogol 3350.

PEG is present in the pharmaceutical preparations of the invention in an amount and in a concentration necessary to achieve pharmaceutical efficacy in the patient. In the product that contains PEG currently marketed Movicol® for use in adults, each envelope contains 13,125 g of PEG 3350 and adults are instructed to take 1 to 3 sachets per day (i.e., 13,125 g to 39,375 g of PEG daily) for the treatment of constipation. The same total amounts of PEG are also appropriate in the case of compressed pharmaceutical preparations of the present invention for the treatment of constipation. Accordingly, a composition of the invention may comprise more than 5 g of PEG, more preferably more than 10 g of PEG. A composition of the invention may comprise less than 20 g of PEG, more preferably less than 15 g of PEG. A composition of the invention may comprise 5 to 20 g of PEG, preferably 10 to 15 g of PEG, for example, 13,125 g of PEG. A given composition may optionally be presented in a divided dose form so that several smaller units are ingested and the total PEG taken is approximately 10 to 15 g.

A particularly convenient compressed composition is a composition comprising 1.5 to 5.5 g of PEG, preferably 2.0 to 3.3 g of PEG, for example, 2.5 g or 2.625 g of PEG. The patient would be advised to take 3 to 5 of such tablets to chew or swallow to constitute 10 to 15 g of PEG for a full dose.

Alternatively, two, three or four dosage units may be appropriate, so that two, three or four dosage units are taken at the same time to constitute the effective dose. Thus, a dosage unit composition having half a dose may comprise 2 to 10 g of PEG, preferably 5 to 7.5 g of PEG, for example, 6,563 g of PEG. Patients are advised to take 2 to 6 of such unit doses of composition per day, so that they receive from 13,125 g to 39,375 g of PEG per day. Similarly, a dosage unit composition having one third of a dose may comprise from 1.67 to 6.67 g of PEG, preferably from 3.33 to 5 g of PEG, for example, 4,375 g of PEG. Patients are advised to take 3 to 9 of such unit doses of composition per day, so that they receive from 13,125 g to 39,375 g of PEG per day. Similarly, a dosage unit composition having a quarter of a dose may comprise 1 to 5 g of PEG, preferably 2.5 to 3.75 g of PEG, for example, 3,281 g of PEG. Patients are advised to take 4 to

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12 such unit doses of composition per day, so that they receive from 13,125 g to 39,375 g of PEG per day.

For the treatment of fecaloma, also known as faecal retention, adults are instructed to take 6 to 10 sachets of Movicol® (properly dissolved in water) per day (i.e., 78.75 g to 131.25 g PEG per day). The number of divided doses of the composition of the invention that are appropriate are analogous to those known in the art that provide similar amounts of PEG, that is, for example, 15 to 65 doses of a composition of the invention comprising 2 to 5 g, for example, 4 g, of PEG, so that the patient receives from 78.75 g to 131.25 g of PEG per day.

Pediatric products currently on the market comprise smaller amounts of PEG than their adult counterparts. For example, Movicol® for the treatment of fecaloma in children (sold under the brand name Movicol Paediatric Plain) contains 6,563 g of PEG 3350 with instructions to prepare up to 62.5 ml of solution in water. For pediatric use, the half dose form for the adult mentioned above may be suitable as a full dose. Thus, a composition of the invention for pediatric use may comprise from 2 to 10 g of PEG, more preferably from 5 to 7.5 g of PEG, for example, 6,563 g of PEG. Pediatric patients with fecaloma are advised to take 2 to 12 of such composition units per day, depending on their age. It is common to treat pediatric fecaloma by taking a cycle of Movicol Paediatric Plain for 7 days with increasing doses as the week progresses. It may be advised that a child of 2-4 years of age take 2 doses of the composition of the invention on the first day, increasing to 8 doses on the 7th day, while it may be advised that a child from 5 to 11 years of age Take 4 doses on the first day, increasing to 12 doses on the 7th day.

For colon cleansing, the currently marketed compositions mentioned in the previous introduction are administered in amounts so that the patient receives in the region of 200 to 300 g of PEG in one dose. Similar amounts of PEG are also suitable in the case of compressed pharmaceutical preparations of the present invention for colon cleansing. Accordingly, a composition of the invention may comprise 200 to 300 g of PEG. A given composition may optionally be presented in a divided dose form, so that two, three

or more doses presented are taken at the same time to constitute the effective dose. Such divided dose forms may provide an appropriate fraction of the total dose. In the case where the composition of the invention is provided in a form comprising from 5 to 7.5 g of PEG, for example, 6.563 g of PEG, the patient would be advised to take 25 to 60 of the units of composition. It may be preferable to dissolve the compressed pharmaceutical composition in water before taking the composition.

A pharmaceutical composition of the present invention comprises one or more electrolytes. Polyethylene glycol is considered to be effective as a laxative by virtue of its osmotic action in the intestine. Polyethylene glycol is not absorbed by the intestine to any significant degree. When taken on its own, polyethylene glycol has an electrolyte filter effect, and thus can lead to a decrease in electrolyte levels in the patient. Accordingly, it is preferred that the compositions of the invention comprise one or more electrolytes. Sodium ions and potassium ions are particularly suitable. Those ions may be present in the form of any suitable salt, for example, such as their salts of chloride, bicarbonate, sorbate, benzoate, acetate, carbonate, citrate, fumarate, gluconate, malate, nitrate, phosphate, succinate, sulfate or tartrate. Chloride and bicarbonate salts are particularly preferred, for example, sodium chloride, potassium chloride and sodium bicarbonate.

Preferably, the electrolytes are selected from sodium chloride, sodium bicarbonate or potassium chloride. Most preferably, a composition of the invention comprises all these electrolytes.

In a preferred formulation comprising 13,125 g of polyethylene glycol in one dose, sodium chloride is preferably present in an amount of 0.1 to 1.0 g, more preferably 0.2 to 0.6 g, for example, 0 , 3 to 0.5 g, for example, 0.3507 g. For compositions comprising different amounts of polyethylene glycol, the amounts of sodium chloride are altered in proportion to the amount of polyethylene glycol present.

In a preferred formulation comprising 2.5 g of polyethylene glycol in one dose, sodium chloride is preferably present in an amount of 0.01 to 0.2 g, more preferably 0.03 to 0.11 g, for example, from 0.05 to 0.09 g, for example, 0.0668 g.

In a preferred formulation comprising 13,125 g of polyethylene glycol in one dose, sodium bicarbonate is preferably present in an amount of 0.05 to 0.5 g, more preferably 0.1 to 0.3 g, for example, 0 , 15 to 0.25 g, for example, 0.1785 g. For compositions comprising different amounts of polyethylene glycol, the amounts of sodium bicarbonate are altered in proportion to the amount of polyethylene glycol present.

In a preferred formulation comprising 2.5 g of polyethylene glycol in one dose, sodium bicarbonate is preferably present in an amount of 0.01 to 0.1 g, more preferably 0.02 to 0.06 g, for example, from 0.03 to 0.05 g, for example, 0.0340 g.

In a preferred formulation comprising 13,125 g of polyethylene glycol in one dose, potassium chloride is

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preferably present in an amount of 0.01 to 0.15 g, more preferably 0.02 to 0.1 g, for example, 0.03 to 0.06 g, for example, 0.0466 g. For compositions comprising different amounts of polyethylene glycol, the amounts of potassium chloride are altered in proportion to the amount of polyethylene glycol present.

In a preferred formulation comprising 2.5 g of polyethylene glycol in one dose, potassium chloride is preferably present in an amount of 0.002 to 0.03 g, more preferably 0.004 to 0.019 g, for example, 0.008 to 0, 01 g, for example, 0.00888 g.

Compressed pharmaceutical compositions of the invention may include sodium sulfate.

In a preferred formulation comprising 13,125 g of polyethylene glycol in one dose, sodium sulfate may be present in an amount of 0.2 to 2 g, more preferably 0.5 to 1.6 g, for example, 0, 7 to 1.3 g, for example, 0.9375 g.

In a preferred formulation comprising 2.5 g of polyethylene glycol in one dose, sodium sulfate is preferably present in an amount of 0.04 to 0.5 g, more preferably 0.1 to 0.3 g, for example , from 0.15 to 0.25 g, for example, 0.179 g

The compressed pharmaceutical compositions of the invention may comprise 5 to 20 g of PEG with a molecular weight of 2500 to 4500, 0.1 to 1.0 g of sodium chloride, 0.05 to 0.5 g of sodium bicarbonate, 0 , 01 to 0.15 g of potassium chloride, and optionally 0.2 to 2 g of sodium sulfate.

The compressed pharmaceutical compositions of the invention may comprise 1.5 to 5.5 g of PEG with a molecular weight of 2500 to 4500, 0.0401 to 0.147 g of sodium chloride, 0.0204 to 0.0748 g of sodium bicarbonate , 0.00533 to 0.0195 g of potassium chloride, and optionally 0.107 to 0.393 g of sodium sulfate.

The compressed pharmaceutical compositions of the invention may comprise ascorbic acid or an ascorbate salt.

Compressed pharmaceutical compositions of the invention may include one or more pharmaceutically acceptable excipients, in particular compression excipients. Suitable excipients include magnesium stearate, cellulose and cellulose derivatives, starch and starch derivatives, lactose and lactose derivatives, dextrates, manitoles and sorbitols. Particularly, in the case of an excipient selected from dextrates, manitoles and sorbitols, the compositions may have been spray dried during their manufacture.

The compressed pharmaceutical compositions of the invention preferably do not comprise other active components, other than PEG. In one embodiment, the compressed pharmaceutical compositions of the invention do not comprise other components with laxative activity.

The compressed pharmaceutical compositions of the invention preferably comprise one or more sweeteners. Artificial or naturally derived sweeteners can be used alone or in a mixture. Suitable sweeteners include, but are not limited to, saccharin, sodium saccharin, sodium cyclamate, acesulfame potassium, thaumatine, neohesperidine dihydrocalcone, ammonium glycyrrhizinate and aspartame. The sweetener may constitute between about 0.01 to 1.0% by weight of the final composition, more preferably about 0.025 to 0.25% by weight, for example, 0.07 to 0.08% in weight. If two sweeteners are used in admixture, the ratios between the two sweeteners may be in the range of about 1:10 to 10:11 by weight.

The compressed compositions of the invention preferably comprise one or more flavorings. Suitable flavors are available from International Flavors & Fragrances Inc. (IFF (GB) Ltd, Duddery Hill, Haverhill, Suffolk, CB9 8LG, United Kingdom) and include flavors commonly used in foods and pharmaceuticals. Examples of suitable flavorings include the raspberry and lemon aroma, lemon aroma, lemon / lime aroma, cola aroma and orange aroma. The amount of flavoring needed to achieve a tasty flavor depends on the identity of the flavoring. Normally, 0.1 to 20% by weight of flavoring is appropriate. Preferably from 1.0% to 15% by weight of flavoring is used. The exact amount of flavoring that is appropriate depends, among other things, on the intensity of the flavoring used. For example, if orange flavoring powder is used, an appropriate amount is 10 to 12% by weight. If glue powder is used, an appropriate amount is 4 to 5% by weight of powder. An aroma enhancer may be used, in addition to a flavoring. Aroma enhancers include citric acid.

A salt masking agent can also be used. Examples of salt masking agents include sodium saccharide (E954), gum arabic (E414), aspartame (E951) and neohesperidine dihydrocalcone (E0959) or mixtures thereof. The amount of salt masking agent necessary to achieve a tasty taste depends on the intensity of the agent. Normally, from 1 to 6% by weight of salt masking agent is appropriate. Preferably from 2% to 5% by weight of salt masking agent is used, particularly from 3 to 4% by weight. The exact amount of flavoring that is appropriate depends on the intensity of the

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masking of used salt.

Preferred compositions according to the invention are those comprising 5 to 20 g of PEG with a molecular weight of 2500 to 4500, 0.2 to 0.6 g of sodium chloride, 0.1 to 0.3 g of sodium bicarbonate, 0 02 to 0.1 g of potassium chloride, an excipient of, for example, magnesium stearate and microcrystalline cellulose, 0.002 to 0.05 g of potassium acesulfame, a flavoring and a salt masking agent.

Alternative preferred compositions according to the invention are those comprising 1.0 to 5 g of PEG with a molecular weight of 2500 to 4500, 0.04 to 0.15 g of sodium chloride, 0.02 to 0.075 g of sodium bicarbonate, 0.004 to 0.025 g of potassium chloride, an excipient of, for example, magnesium stearate and microcrystalline cellulose, 0.0004 to 0.0125 g of potassium acesulfame, a flavoring and a salt masking agent.

The compressed pharmaceutical compositions of the invention are for oral administration. Preferably, the compressed pharmaceutical compositions of the invention are in the form of tablets, pellets, pills or lozenges. In one embodiment, they can be chewable or swallowable.

The invention also provides a compressed pharmaceutical composition comprising polyethylene glycol of molecular weight from 2000 to 4500 and one or more electrolytes selected from sodium chloride, sodium bicarbonate and potassium chloride, for the treatment of constipation, fecaloma, fecal retention, gas and intestinal cramps , or flatulence; or for orthostatic lavage, bowel movement or colon cleansing.

The compressed pharmaceutical compositions of the invention have the additional advantages that they can be manufactured and packaged in a convenient manner. For example, manufacturing and packaging techniques used in the manufacture of pharmaceutical tablets can be employed.

The compressed pharmaceutical compositions of the invention are usually prepared by mixing together the components in dry powder form and compressing them in the desired form.

The invention also provides a method of preparing a compressed pharmaceutical composition comprising the steps of:

a) mixing together polyethylene glycol of molecular weight from 2000 to 4500 with one or more electrolytes and optionally one or more components selected from: one or more sweeteners; one or more flavorings; one or more excipients; ascorbic acid and / or an ascorbate salt; sodium sulfate; and optionally additional components; Y

b) compress the mixture into a pharmaceutical compressed composition.

Methods of preparing compressed pharmaceutical compositions are well known in the art, for example, see Rudnic, E., and Schwartz, J.B. Oral Solid Dosage Forms, Chapter 92, Tablets, p. 1615-1641, in Remington's, 19th ed.

The invention also provides a method of treating constipation, fecaloma, fecal retention, gas and intestinal cramps, or flatulence, which comprises administering an effective dose of a compressed pharmaceutical composition according to the invention to a mammal in need of such treatment. Preferably, the mammal is a human being. The invention particularly provides a method of treating constipation in a mammal.

The invention also provides a method of cleaning the colon of a mammal by administering an effective amount of a compressed pharmaceutical composition according to the invention. Preferably, the mammal is a human being.

The invention further provides the use of a compressed pharmaceutical composition according to the invention for the manufacture of a medicament for the treatment of constipation, fecaloma, fecal retention, gas or intestinal cramps, or flatulence in a mammal. The invention also provides the use of a compressed pharmaceutical composition according to the invention for the manufacture of a medicament for cleaning the colon.

The invention further provides the use of a compressed pharmaceutical composition according to the invention for the manufacture of a medicament for the treatment of constipation.

The invention further provides the use of PEG for the manufacture of a medicament for the treatment of constipation, said medicament being a pharmaceutical compressed composition.

The following non-limiting examples illustrate the invention.

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Examples

A. Sample formulations:

Formulation 1

The si were mixed

Powder-shaped component guides:

Macrogol 3350

13,125 g

Sodium chloride

0.3507 g

Sodium bicarbonate

0.1785 g

Potassium chloride

0.0466 g

Acesulfame K

0.010 g

Formulation 1a additionally included orange flavoring powder (IFF No. 17.02.1247, 11% by weight in the powder mixture, i.e. 1.508 g) and salt masking agent (3.45% by weight in the powder mixture , that is, 0.473 g). Formulation 1b additionally included cola flavoring powder (IFF No. 15.02.3366, 4.4% by weight in the powder mixture, i.e. 0.603 g) and salt masking agent (3.45% by weight in the mixture powder, ie 0.473 g). Formulation 1c additionally included raspberry and lemon flavoring powder (IFF No. 10.84.8966, 1.5% by weight in the powder mixture, i.e. 0.206 g, NB: the raspberry and lemon flavoring powder includes masking agent the salt).

The salt masker was the product marketed by IFF under the number 13.63.0145 comprising 6.8% sodium saccharide (E954), 4.6% gum arabic (E414), 4.1% aspartame (E951) and 0.09% neohesperidine dihydrocalcone (E0959) and natural lactose and flavoring substances of an identical nature.

The powder mixture was then compressed.

Formulation 2

The following components were mixed in powder form:

Macrogol 3350 13,125 g

Sodium Chloride 0.3507 g

Baking soda 0.1785 g

Potassium Chloride 0.0466 g

Acesulfame K 0.010 g Formulation 2a additionally included orange flavoring powder (IFF No. 15.02.9804, 2% by weight in the powder mixture, i.e. 0.264 g), salt masking agent (4% by weight in the mixture powder, i.e. 0.548 g) and effervescent powder (IFF No. 17.43.6575, 10% by weight in the powder mixture, i.e. 1.371 g). Formulation 2b additionally included cola flavoring powder (IFF No. 15.02.3366, 1.5% by weight in the powder mixture, i.e. 0.206), salt masking agent (4% by weight in the powder mixture, that is, 0.548 g) and effervescent powder (IFF No. 17.43.6575, 10% by weight in the powder mixture, that is, 1,371 g).

The salt masker was the product marketed by IFF under the number 13.63.0145 comprising 6.8% sodium saccharide (E954), 4.6% gum arabic (E414), 4.1% aspartame (E951) and 0.09% neohesperidine dihydrocalcone (E0959) and natural lactose and flavoring substances of an identical nature.

The powder mixture was then compressed.

Formulation 3

The following components were mixed in powder form:

Macrogol 3350 13,125 g

Sodium Sulfate 0.9375 g

Sodium Chloride 0.3507 g

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Sodium bicarbonate

0.1785 g

Potassium chloride

0.0466 g

Acesulfame K

0.010 g

Formulation 3a additionally included orange flavoring powder (IFF No. 17.02.1247, 11% by weight in the powder mixture, i.e. 1.508 g) and salt masking agent (3.45% by weight in the powder mixture , that is, 0.473 g). Formulation 3b additionally included cola flavoring powder (IFF No. 15.02.3366, 4.4% by weight in the powder mixture, i.e. 0.603 g) and salt masking agent (3.45% by weight in the mixture powder, ie 0.473 g). Formulation 3c additionally included raspberry and lemon flavoring powder (IFF No. 10.84.8966, 1.5% by weight in the powder mixture, i.e. 0.206 g, NB: the raspberry and lemon flavoring powder includes masking agent the salt).

The salt masker was the product marketed by IFF under the number 13.63.0145 comprising 6.8% sodium saccharide (E954), 4.6% gum arabic (E414), 4.1% aspartame (E951) and 0.09% neohesperidine dihydrocalcone (E0959) and natural lactose and flavoring substances of an identical nature.

The powder mixture was then compressed.

B. Taste tests

Acceptability of the compositions of the invention was compared with prior art compositions. The prior art compositions used were Movicol® preparations, obtained from Norgine Limited (Chaplin House, Widewater Place, Moorhall Road, Harefield, Middlesex UB9 6NS, RU). It is supplied as a powder in sachets, each containing 13.8 g of powder. Each envelope contains the following components: Macrogol (polyethylene glycol) 3350: 13,125 g, sodium chloride: 350.7 mg; sodium bicarbonate: 178.5 mg; and potassium chloride: 46.6 mg. The contents of an envelope were made up to 125 ml of solution by the addition of water.

In the taste tests, six healthy volunteers were given both one that served as Movicol preparation and one 1c formulation serving. Each of the six said volunteers preferred the tablet to the beverage solution.

The present invention also relates to the following sections:

§one. A compressed pharmaceutical composition comprising

-polyethylene glycol of molecular weight from 2000 to 4500, in which the polyethylene glycol constitutes from 80 to 99.5% by weight of the composition,

-one or more electrolytes

-for the treatment of constipation, fecaloma, fecal retention, gas and intestinal cramps, or flatulence; or for orthostatic lavage, bowel movement or colon cleansing.

§2. A pharmaceutical composition as in §1, in which the electrolytes are selected from sodium chloride, sodium bicarbonate or potassium chloride.

§3. A pharmaceutical composition as in §1 or 2 which also comprises one or more sweeteners.

§4. A pharmaceutical composition as in any one of §1 to 3 which further comprises one or more flavorings.

§5. A pharmaceutical composition as in any one of §1 to 4 comprising 5 to 20 g of PEG with a molecular weight of 2500 to 4500, 0.1 to 1.0 g of sodium chloride, 0.05 to 0.5 g of sodium bicarbonate, 0.01 to 0.15 g of potassium chloride, and optionally 0.2 to 2 g of sodium sulfate.

§6 A pharmaceutical composition as in any one of §1 to 4 comprising from 1.5 to 5.5 g of PEG with a molecular weight of 2500 to 4500, 0.0401 to 0.147 g of sodium chloride, 0.0204 to 0, 0748 g of sodium bicarbonate, 0.00533 to 0.0195 g of potassium chloride, and optionally 0.107 to 0.393 g of sodium sulfate.

§7 A method of preparing a compressed pharmaceutical composition as described in §1 comprising the steps of:

a) mixing together polyethylene glycol of molecular weight from 2000 to 4500 with one or more electrolytes and optionally one or more components selected from: one or more sweeteners; one or more flavorings; one or more excipients; ascorbic acid and / or an ascorbate salt; sodium sulfate; Y

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optionally additional components; Y

b) compress the mixture into a pharmaceutical compressed composition.

§8 A treatment procedure for constipation, fecaloma, fecal retention, gas and intestinal cramps,

or flatulence in a mammal by administration of an effective amount of a compressed pharmaceutical composition as in any one of §1 to 6.

§9 A method of cleaning a mammal's colon by administering an effective amount of a compressed pharmaceutical composition as in any one of §1 to 6.

§10 Use of a compressed pharmaceutical composition as in any one of §1 to 6 for the manufacture of a medicament for the treatment of constipation, fecaloma, fecal retention, gas or intestinal cramps,

10 or flatulence.

§eleven. Use of a compressed pharmaceutical composition as in any one of §1 to 6 for the manufacture of a medicament for cleansing the colon.

§12 A unit dosage constipation treatment composition comprising a compressed pharmaceutical composition as in any one of §1 to 5 in an amount of 5 to 20 g of polyethylene glycol,

15 optionally in the form of divided doses.

§13 A unit dosage constipation treatment composition comprising a compressed pharmaceutical composition as in any one of §1 to 4 in an amount of 200 to 300 g of polyethylene glycol, optionally in the form of divided doses.

Claims (15)

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one.

A compressed pharmaceutical composition comprising

-polyethylene glycol of molecular weight from 2000 to 4500, in which the polyethylene glycol constitutes from 80 to 99.5% by weight of the composition, and -one or more electrolytes.

2.

A pharmaceutical composition according to claim 1, wherein the electrolytes are selected from sodium chloride, sodium bicarbonate and potassium chloride.

3.

A pharmaceutical composition according to claim 1 or 2, further comprising one or more excipients.

Four.

A pharmaceutical composition according to any one of claims 1 to 3, further comprising one or more sweeteners.

5.

A pharmaceutical composition according to any one of claims 1 to 4, further comprising one or more flavorings.

6.

A pharmaceutical composition according to any one of claims 1 to 5, further comprising citric acid.

7.

A pharmaceutical composition according to any one of claims 1 to 6, further comprising ascorbic acid or an ascorbate salt.

8.

A pharmaceutical composition according to any one of claims 1 to 7, wherein the polyethylene glycol has a molecular weight of 3350 or 4000.

9.

A pharmaceutical composition according to any one of claims 1 to 8, further comprising sodium sulfate.

10.

A pharmaceutical composition according to any one of claims 1 to 8, comprising 5 to 20 g of PEG with a molecular weight of 2500 to 4500, 0.1 to 1.0 g of sodium chloride, 0.05 to 0.5 g of sodium bicarbonate, 0.01 to 0.15 g of potassium chloride, and optionally 0.2 to 2 g of sodium sulfate.

eleven.

A pharmaceutical composition according to claim 10, comprising 13,125 g of polyethylene glycol.

12.

A pharmaceutical composition according to any one of claims 1 to 8, comprising from 1.5 to 5.5 g of PEG with a molecular weight of 2500 to 4500, 0.0401 to 0.147 g of sodium chloride, 0.0204 to 0 , 0748 g of sodium bicarbonate, 0.00533 to 0.0195 g of potassium chloride, and optionally 0.107 to 0.393 g of sodium sulfate.

13.

A pharmaceutical composition according to claim 12, comprising 2.5 g of polyethylene glycol.

14.

A pharmaceutical composition according to any one of claims 1 to 10, in unit dosage form having an amount of 5 to 20 g of polyethylene glycol, optionally in the form of a divided dose; or a pharmaceutical composition according to any one of claims 1 to 9, in unit dosage form having an amount of 200 to 300 g of polyethylene glycol, optionally in the form of a divided dose.

fifteen.

A pharmaceutical composition according to any one of claims 1 to 14, for use as a medicament.

10